The goals of this project are to define the roles of human retroviruses and host cellular immune responses directed at these agents in chronic- progressive neurologic disease. The association of the human T lymphotropic virus type I (HTLV-I) and the disorder known as HTLV-I- associated myelopathy/tropical spastic paraparesis (HAM/TSP) is being used as the model system for an understanding of the pathogenic mechanism(s) involved in human retroviral diseases of the central nervous system (CNS). These investigations involve the virologic and molecular characterization of the agent(s) isolated from patients with neurologic disease, because unique features of these viruses may contribute to the pathogenesis of CNS disease. Long-term T and B cell lines expressing endogenous human retrovirus have been established from affected individuals and have been used to characterize these molecular and virologic aspects of these agents. The presence of human retrovirus in the CNS of these patients is being assessed by in situ hybridization. Host cellular immune responses to various strains of HTLV-I are characterized because immunopathologic mechanisms are believed to be directly involved in the pathogenesis of HAM/TSP. Focus is being placed on the role of cytotoxic T cells (CTL) in the pathogenesis of HAM/TSP because circulating CTL have been demonstrated from the peripheral blood and cerebrospinal fluid of HAM/TSP patients, but not from HTLV-I carriers. The precursor frequency of these CTL is being assessed by limiting dilution studies. Lastly, an association has been documented between HTLV-II. a closely related retrovirus to HTLV-I, and a chronic- progressive neurologic disease clinically indistinguishable from HAM/TSP.